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Propylthiouracil-induced hemolytic anemia.

Propylthiouracil (PTU)-induced hemolytic anemia is extremely rare. We reported a case of Graves' disease with these unusual clinical manifestations. A 41-year-old female presented with recurrent attacks of severe hemolytic anemia after PTU therapy. Sugar water test and erythrocytes osmotic fragility test revealed no cellular membrane defect of red blood cells. Antinuclear antibody, direct and indirect Coombs' tests were all negative and glucose-6-phosphate dehydrogenase activity was also within normal limits. PTU was not discontinued promptly due to unrecognizableness of such a rare case until two months later with recurrent attacks of severe hemolytic anemia. 1-131 therapy was performed on suspicion of related hemolytic anemia. Unfortunately, challenge of PTU occurred incidentally after discontinuation of PTU followed by severe hemolytic anemia. The diagnosis of PTU-induced hemolytic anemia was established thereafter. A MEDLINE search revealed only one such case reported in English literature. This is the first case report in Taiwan. It should be kept in mind that hemolytic anemia may be a rare complication of PTU therapy.

Adult↗

[Microspherocytosis. Erythroid profile and its relation with different laboratory tests].

Hereditary spherocytosis (HS) is a congenital and hemolytic anemia characterized by the presence of microspherocytes on the peripheral blood film and negative Coombs test. Although HS is a heterogeneous syndrome in terms of clinical severity, inherents and underlying molecular defects (deficiency of membrane skeleton proteins), typical HS has a dominant inheritance pattern and presents anemia, jaundice and splenomegaly. The purpose of this study was to present our experience and to establish the relationship between hematological and biochemical parameters and osmotic fragility and autohemolysis, all of them considered as traditionally available tests. In our environment, HS is the second most common inherited anemia after beta thalassemia trait. The diagnosis was based on osmotic fragility measurements, autohemolysis test and microspherocytes in 47 patients (45 of latin, 2 of saxon origin); 12 patients had a negative family history. Mean values: RBC (x 10(12)/L) and Hb (g/dL): children (22): 3.84/10.5; adults (25): female (13): 3.54/10.59; masculine (12): 4.65/13.15. Autohemolysis (average %) was very much increased (15.54) and it was corrected by the addition of glucose (4.07). Median osmotic fragility (average g/dL) was increased in both fresh (0.48) and incubated blood (0.65). 76.5% children and 26.7% adults had absence of haptoglobin. Reticulocytes, indirect bilirubin and LDH were increased (average values 336.35 x 10(9)/L, 36.25 mmol/L and 236.48 UI/L, respectively). Microcytosis, spherocytosis, polycromatophylia, acanthocytosis, basophilic stippling, pincered cells were observed in 43, 41, 41, 12, 11, 1 patients respectively. Morphologic alterations were more marked in children. The laboratory findings seemed more a consequence of microcytosis than of spherocytosis.

Adolescent↗

An enzyme-labelled immunosorbent assay for Brucella abortus antibodies.

An enzyme-linked immunosorbent assay (ELISA) for Brucella abortus antibody was compared with direct agglutination, complement fixation and Coombs tests in studies of 112 sera. Of these, 15 gave positive results by ELISA tests which included the 13 sera that gave positive results in the other tests. The assay aided recognition of four groups: (i) sera with very high levels of specific IgG and significant levels of IgM and IgA from patients with acute brucellosis; (ii) sera with high levels of IgG only from patients with chronic brucellosis; (iii) sera with low levels of IgG only, representing residual antibody; (iv) sera with little or no brucella-specific antibody. ELISA was antibody-class specific, and the results were more readily interpreted than conventional seological data. Moreover, ELISA was more sensitive, more rapid and simpler than the battery of agglutination, Coombs and complement-fixation tests commonly used.

Antibodies, Bacterial↗

[Multicentric Castleman's disease accompanied with both lymphoid interstitial pneumonia and interstitial nephritis].

A 60-year old man admitted in November, 1991 because of hyperproteinemia. He had shown a gradual increase in serum levels of gamma-globulin since 1981, and idiopathic plasmacytic lymphadenopathy with hyperimmunoglobulinemia was diagnosed in 1989 when he was admitted to another hospital because of persistent swelling of bilateral inguinal lymph nodes since 1986. Multiple swelling of lymph nodes was observed in the right supraclavicle fossa, the left axillary and bilateral inguinal region, and diffuse reticulo-nodular shadows were observed on his chest roentogenogram. Other laboratory findings were as follows; erythrocyte sedimentation rate 143 mm/hr, CRP 3+, Hb 9.4 g/dl, TP 13.7 g/dl with 69.4% of beta-gamma bridge, BUN 21.1 mg/dl, creatinine 1.6 mg/dl, PaO2 77.6 mmHg, plasma cell count in bone marrow 6.4% and positive tests for autoantibodies such as rheumatoid factor, anti-DNA antibody, anti-smooth muscle antibody, and direct Coombs test. Serum interleukin-6 (IL-6) level increased to 259 pg/ml and IL-1 beta was 39.1 pg/ml. Specimens of both transbronchial lung biopsy and fine-needle kidney biopsy revealed a marked infiltration of lymphocytes and plasma cells into interstitial regions of lung and kidney. We reported here a case of multicentric Castleman's disease (MCD) who also demonstrated lymphoid interstitial pneumonia and interstitial nephritis. The present study suggests that some cytokines including IL-6 and IL-1 beta may be closely related to the pathophysiology of MCD.

Castleman Disease↗

[An autopsy study of immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma in a patient previously treated with chemotherapy in colon cancer].

A 77-year-old man was admitted to our hospital, due to systemic lymph node swelling. Nine months before his admission, he had been given a right hemicolonectomy for a colon cancer, that had been followed by chemotherapy (MMC and Tegafur). Laboratory testing revealed these findings: RBC 217 x 10(4)/mm3, Hb 8.3 g/dl, haptoglobin less than 10 mg/dl, positive Coombs test, cold hemagglutinin titer, 1:512, and polyclonal hyper r-globulinemia. A biopsy of a lymph node specimen exhibited the histological appearance of an IBL-like T-cell lymphoma described by Shimoyama et al. Although treatment with prednisolone was started for autoimmune hemolytic anemia, the patient died of severe anemia two months after the appearance of his lymph node symptoms.

Aged↗

[Paroxysmal nocturnal hemoglobinuria. Diagnosis aided by a monoclonal antibody directed against the decay accelerating factor glycoprotein].

The laboratory diagnosis of paroxysmal nocturnal haemoglobinuria (also called Marchiafava-Micheli disease) is based on the sensitivity of the patient's red cells to complement-induced lysis. In view of the clonal expression of the disease, haemolysis tests are difficult to interpret when the abnormal red cell population is small. The sensitivity of abnormal red cells to haemolysis is due to the absence of proteins attached to the cell membrane by a phosphatidyl-inositol link, which intervene in the regulation of the complement-induced lysis mechanism. Using a monoclonal antibody directed against one of these proteins, the decay accelerating factor (DAF, protein CD 55), makes it possible to diagnose paroxysmal nocturnal haemoglobinuria. DAF expression on patients' blood cells was measured by quantitative agglutination and by indirect flow cytometry. The agglutination test using polybren is a fast detection method, but it may be uninterpretable, notably in cases with positive antiglobulin (Coombs') test. In contrast, DAF expression measured by indirect flow cytometry correlates perfectly with measurement of red cell sensitivity by haemolysis tests. Using the monoclonal antibody by indirect flow cytometry is the method of choice to confirm the diagnosis of paroxysmal nocturnal haemoglobinuria and to measure the proportions of normal and abnormal red cells in case of haematological disorder.

Adolescent↗

Chlorpromazine-induced lupus anticoagulant and associated immunologic abnormalities.

Chronic administration of chlorpromazine is associated with the development of a lupus-like circulating anticoagulant and a variety of immunological abnormalities. The prevalence of these findings was studied in 123 psychiatric patients. The anticoagulant was present in 11 of 30 patients receiving chlorpromazine (CPZ), in none of 17 patients who had been off phenothiazine therapy for over a year and in none of 53 controls. It was also seen in 5 of 13 patients who had been switched from CPZ to another phenothiazine even after several years being off CPZ. The anticoagulant was characterized by prolongation of the partial thromboplastin time, thromboplastin dilution test, and Russell's viper venom time. Washed frozen platelets partially corrected the abnormality induced by the anticoagulant. In all but one case the anticoagulant was associated with positive antinuclear antibody test and/or increased serum IgM. Six of 16 patients also had decreased complement levels, and two had a positive direct Coombs' test. None of these patients manifested bleeding, hemolysis, splenomegaly, or other clinical features of systemic lupus erythematosus.

Adolescent↗

[Combined use of rose Bengal and indirect immunofluorescence in the diagnosis of brucellosis].

In the present prospective study we have evaluated the sensitivity, specificity and predictive value of the Bengal rose and indirect immunofluorescence (IIF) in 122 patients with a bacteriological diagnosis of brucellosis. The sensitivity of the Bengal rose was 95.79% and its specificity 98.43%. IIF had a sensitivity of 68.80% and a specificity of 100% when the polyvalent anti-IgS conjugate was used. The combined parallel use of Bengal rose and IIF-IgS resulted in a sensitivity of 89.17% and a specificity of 100%. There was a good correlation between Bengal rose and serum agglutination test (r = 0.72); on the contrary, there were not good correlations between the fluorescent conjugates and Bengal rose, agglutination and Coombs test. In conclusion, the combined use of Bengal rose as a screening test and IIF as a confirmation study is a good diagnostic strategy for human brucellosis.

Agglutination Tests↗

[Collagen disease. Autoimmune disease].

Collagen disease is systemic autoimmune disease and consists of a lot of diseases with each clinical entity. for exact diagnosis, it is important to choose essential laboratory tests for the patient suspected of collagen disease in daily primary medical care. A guideline for the use of clinical laboratory tests for patients with collagen disease was proposed by the Japan Society of Clinical Pathology. This guideline was discussed repeatedly by subcommittee members of "the uses of clinical laboratory tests in daily primary medical care" and published on September of 1990. When the clinicians are suspected of the collagen disease from detailed history taking and physical examination, they must precisely interpret results of the essential laboratory tests. Urinalysis, hematology, ESR and CRP and Biochemistry show characteristic findings in the collagen disease, respectively. If further suspicion of the collagen disease is intensive, the clinicians proceed with the primary screening tests for collagen disease; rheumatoid factor, ANF, anti DNA antibody, LE test, STS and CH50. Finally, specific tests for each collagen disease are carried out to define the diagnosis; e.g. LE cell, anti-Sm antibody, IC, Coombs test and biopsy of kidney for SLE. This paper is presented on the intention of the guideline of clinical laboratory tests for the collagen disease and its issues. As it passed 4 years after published, this guideline should be more discussed and revised.

Autoimmune Diseases↗

[Cold agglutinin with anti-B specificity in an A1B subject].

A high titre cold autoagglutinin with anti-B specificity was found in the serum of an A1B group individual. It was associated with a low titre anti-I. This anti-B agglutinated most cells having a B antigen (normal B, A1B, A2B, from adult and cord bloods, B3), but failed to agglutinate Bx Cis-AB and Bh cells. Nevertheless, all these cells absorbed the anti-B SER at low temperatures. Fixation elution tests were also positive on the patient's cells and three consecutive absorptions on these cells completely removed the anti-B activity. The Coombs test was positive with anti-complement anti-globulin when the cells were sensitized by the serum at 4 degrees C. It was negative when the cells were sensitized at 37 degrees C. The patient did not show any sign of haemolysis. The anti-B was a IgM Kappa. Its reaction with normal B cells had an enthalpy change of - 36-000 cal./mole, i.e. very different from O ANd A individuals, but similar to that of the erythrocytic I antigen - anti-i antibody reaction. Quantitative measurements showed the erythrocyte B antigen similar to that of control A1B cells.

ABO Blood-Group System↗

Anti-A antibody transfused with non-group-specific platelets. Serological abnormalities.

In 1979 we identified six patients in blood group A who were given non-group-specific platelets and who had difficulties in pretransfusion testing because of passively acquired antibodies to their own A antigen. In all six, results of earlier pretransfusion testing were unremarkable. Postplatelet transfusion findings consisted of the following: (1) negative result of screening for unexpected antibodies, (2) positive result from direct antiglobulin (Coombs') test, (3) incompatible cross match with group A RBCs, and (4) detection of anti-A antibody in each patient's serum and eluate. No clinical evidence of hemolysis was present in any of the patients. Identification of passively acquired ABO antibodies and selection of compatible blood can be facilitated by (1) accurate review of transfusion history for administration of non-group-specific blood products, (2) testing of eluate against group A, B, and O RBCs, and (3) cross match of patient's sera against group O donor RBCs.

ABO Blood-Group System↗

Efficacy of immunoserodiagnostic procedures in the recognition of canine immunologic diseases.

Six immunologic tests were conducted on a large population of dogs with a variety of diseases. The test results were analyzed retrospectively and correlated to the clinical and final pathologic diagnoses. The results indicated that rheumatoid factor and the direct antiglobulin (Coombs) test were both sensitive and specific for the diagnoses of canine rheumatoid arthritis and autoimmune hemolytic anemia. The antinuclear antibody test was useful in supporting the diagnosis of systemic lupus erythematosus (SLE) only when both antibody titer and the staining pattern were taken into consideration. The lupus erythematosus cell test was specific but not sensitive when used to confirm a diagnosis of canine SLE. Cellulose acetate serum electrophoresis and immunoelectrophoretic techniques were each useful in supporting the diagnosis of multiple myeloma. Epizootiologic data collected in this study indicated that dogs with primary immunologic disease had a poor prognosis. A female predisposition was observed in cases of canine autoimmune hemolytic anemia and SLE. Ovariectomy seemed to prevent the development of canine SLE.

Agammaglobulinemia↗

Lupus anticoagulant associated syndrome in benign and malignant systemic disease--analysis of ten observations.

The clinical and laboratory findings in seven female patients with primary autoimmune diseases, one female patient with lymphoplasmacytoid (LP) immunocytoma and IgM paraproteinemia, and two male patients with multiple myeloma are described. The common denominator in all patients was a lupus anticoagulant or a closely related coagulation disorder. Recurrent thrombosis was observed in six patients with autoimmune diseases and in two patients with malignant monoclonal gammopathies. Other clinical manifestations included cerebral disorders (four patients with autoimmune disease/two patients with monoclonal gammopathy), repeated obstetric complications (6/1), asymptomatic valvular heart disease (6/1), renal dysfunction (6/2), hepatic involvement (2/2), and arthropathy (2/0). Laboratory investigations revealed a biologic false-positive serological test for syphilis in six patients with autoimmune disease and one with monoclonal gammopathy, antinuclear antibodies (4/0), antibodies against DNA (4/1), and a positive direct Coombs test (3/1) which was accompanied by hemolytic anemia in two patients (1/1). Additionally slight leukocytopenia (2/1) and thrombocytopenia (6/2) were observed; abnormal bleeding was only seen in one patient with severe thrombocytopenia. Other complications characteristic of LP immunocytoma or multiple myeloma were missing. The obvious similarities between the patients with autoimmune diseases and the patients with malignant monoclonal gammopathies suggest analogous pathogenetic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗

A case of myocarditis caused by Mycoplasma pneumoniae.

A 16-year-old girl with myocarditis and hepatitis in the course of mycoplasma pneumoniae infection was reported. She had fever and coughed for ten days prior to admission. At the time of admission infiltrations of the left lower lung field were revealed on the chest X-ray films. The ESR was elevated and CRP+6. There were no leukocytosis and anemia, but S-GOT, S-GPT and LDH were moderately increased. On the 11th day of admission VPC in bigeminy appeared and the third sound was heard. Subsequently biphastic and inverted T waves in leads V2 and V3 and flattening of T waves in leads II and aVF appeared. At the same time, the cardiac shadow was enlarged. Antibody titer to mycoplasma pneumoniae increased to more than 1:640 two weeks after admission and then it decreased gradually. The cold agglutinin test was 1:64 on the 8th day of the disease and then it became normal. ASO, antibodies to DNA and immunoglobulins were normal; ANA, Coombs test and LE test were negative. The abnormal ECG-findings were normalized three months later.

Adolescent↗

An animal model for hemolytic disease of the fetus or newborn in New Zealand white and New Zealand red rabbits: newborn effects.

OBJECTIVE: Our purpose was to study the neonatal effects of red blood cell alloimmunization in a rabbit model. STUDY DESIGN: Eighteen does were alloimmunized to incompatible red blood cells. Does were bred twice, once with a homozygous buck of incompatible blood type and once with a homozygous buck of compatible blood type. Fetal blood sampling was undertaken on day 27 of gestation (term 28 to 31 days). Does were delivered on day 30 and the neonatal pups were anesthetized. Direct cardiac samplings were performed for hemoglobin, reticulocyte count, and direct Coombs' test. Hepatic, splenic, and renal wet weights were measured. RESULTS: Twenty-two pregnancies (12 compatible and 10 incompatible) were studied. Neonatal hemoglobin was higher in the compatible litters (11.1 gm/dL [7.7 to 12.6 gm/dL] vs 4.9 gm/dL [2.1 to 9.1 gm/dL], P <.001), whereas no difference could be detected between the respective reticulocyte counts (34.0/100 red blood cells [27.3 to 36.1/100 red blood cells] vs 32.6/100 red blood cells [26.8 to 43.5/100 red blood cells], P =.55). The direct Coombs' assay was negative in 23 pups from 8 compatible litters and false positive (weakly positive result) in 2 pups of a ninth compatible litter. The Coombs' assay was positive in all 22 incompatible pups tested. Hepatosplenomegaly was noted in affected pups but not in controls. CONCLUSIONS: A disease analogous to human hemolytic disease of the newborn can be induced in the rabbit neonate.

Animals↗

Subcutaneous panniculitis-like T-cell lymphoma with hemophagocytic syndrome successfully treated with cyclosporin A.

A 17-year-old girl previously in good health presented with a 2-month history of recurrent, high-grade fever; general fatigue; anorexia; a 10-kg weight loss; and multiple, painful, reddish skin lesions on the lower abdomen. Some lesions were ulcerated, with an oily yellowish brown discharge. A systemic review was unremarkable other than bleeding from the nose. Her medical and family histories were unremarkable. On examination, the patient was pale, jaundiced, and febrile (temperature of 39 degrees C). She had enlarged lymph nodes in the axillary and inguinal areas. There was moderate hepatosplenomegaly. Local skin examination revealed multiple erythematous, tender, and firm subcutaneous nodules of variable size (1-2 cm) on the lower abdomen. Some nodules were ulcerated, with oily yellowish brown discharge and overlying ecchymosis (Figures 1 and 2). Mucous membranes were free of lesions. Laboratory investigations showed pancytopenia, an elevated erythrocyte sedimentation rate (>80 mm/h), normal renal function tests, abnormal hepatic function tests (alanine aminotransferase 172 U/L, aspartate aminotransferase 229 U/L, alkaline phosphatase 725 U/L, and total bilirubin 100 mmol/L [normal range 0-18 mmol/L]), conjugated bilirubin 45 mmol/L (normal range 0-5 mmol/L), and high triglycerides 855 mg/dL (normal range 20-200 mg/dL). Prolonged prothrombin time, 26 seconds (normal range 13-16 seconds); prolonged activated partial thromboplastin time, 61 seconds (normal range 26-38 seconds); positive disseminated intravascular coagulation studies evidenced by low fibrinogen, 74 mg/dL (normal range 160-350 mg/dL); and positive fibrinogen degradation products were also noted. Throat, midstream urine, and blood culture results were negative. Serologic tests for syphilis, HIV, and hepatitis B and C viruses were negative. Epstein-Barr virus and cytomegalovirus serologic values revealed evidence of past infection. Tuberculin and Coombs tests were negative. The alpha1-antitrypsin level was normal. Antinuclear and anti-smith antibodies, rheumatoid factor, and cryoglobulins were negative. CT showed enlarged lymph nodes in the axillary and inguinal areas, bilateral small pleural effusion, moderate hepatosplenomegaly, severe fatty infiltration of the liver, and thickening of lower abdominal subcutaneous tissue. A liver biopsy showed steatohepatitis. Bone marrow aspirate and trephine were normal. A deep punch biopsy of a nodule from the right lower abdomen revealed lobular panniculitis with atypical lymphocytes and large macrophages with cytophagocytosis ("beanbag" cells) (Figures 3 and 4). Immunohistochemistry showed that these atypical cells were positive for CD3, CD8, granzyme B, and perforin, and negative for CD56. T-cell gene rearrangement studies on skin lesions revealed a monoclonal T-cell receptor (gamma-chain) gene rearrangement, supporting the diagnosis of subcutaneous panniculitis-like T-cell lymphoma. On presentation, the initial treatment included 6 U of fresh frozen plasma, 2 U of packed red blood cells, and 2 g IV fibrinogen for 3 consecutive days. The patient was started on prednisolone 60 mg orally once daily and cyclosporine A 5 mg/kg/d orally in two divided doses. The fever and other systemic symptoms and skin lesions resolved within 2 weeks after the treatment. The prednisolone dose was tapered gradually, and a maintenance dose of cyclosporine A was continued. The patient's condition remained in remission at 12-month follow-up; there was no evidence of clinical relapse.

Adolescent↗

Mechanisms for the removal of senescent human erythrocytes from circulation: specificity of the membrane-bound immunoglobulin G.

Direct antiglobulin (Coombs') tests of erythrocyte (RBC) subpopulations confirmed the presence of membrane-bound immunoglobulin G (IgG) on old (density greater than 1.110) human RBCs but not on the young (density less than 1.110) RBCs. After thermal elution of the bound IgG, this Coombs' reaction was negative, but incubation of thermally eluted IgG (He-IgG) with heat-treated RBCs induced a positive antiglobulin test. A positive direct antiglobulin reaction was also obtained after incubation of heat-treated RBCs with anti-T antibody. Similar results were obtained when young RBCs treated with Vibrio cholerae neuraminidase (VCN) were incubated with anti-T or with IgG eluted by heat from old RBCs. Nevertheless, pre-absorption of heat-eluted IgG with T and/or Tn antigen, did not prevent it from binding to either heat-treated old or VCN-treated young RBCs as assessed by the antiglobulin consumption assay. Pre-treatment of either VCN-treated young or heat-treated old RBCs with anti-T and/or anti-Tn antibodies had no significant effect on the binding of radiolabeled He-IgG (eluted from old RBCs). The results indicate that even though desialylation of the erythrocyte membrane is required for binding of both anti-T-Tn and He-IgG, the specificity and consequently the RBC binding sites for He-IgG and anti-T seem to be different.

Antigens, Tumor-Associated, Carbohydrate↗